Reduced glutathione is a tripeptide constituted of 3 kinds of amino acids (glutamic acid, cysteine and glycine), and has been utilized as a raw material of a pharmaceutical product or health food, as a material having an anti-oxidative function and a detoxification action. In recent years, the development into a wide variety of markets such as beverages, cosmetics and the like has also been expected.
The crystal of reduced glutathione includes two kinds of crystal polymorphs of α-form crystal and β-form crystal (non-patent document 1). The solubility of the α-form crystal, which is an unstable crystal, and that of the β-form crystal, which is a stable crystal, are markedly different, and the saturated solubility at 10° C. is 89 g/L for the α-form crystal and 30 g/L for the β-form crystal (FIG. 1) (FIGURE). Therefore, the β-form crystal having low solubility is associated with problems that it is difficult to process as a raw material and cannot be handled with ease. Furthermore, a needle-like small β-form crystal is inferior to α-form crystal, which is columnar and easily scaled up, in terms of quality and productivity since it is poor in separability from the mother liquor.
In crystal slurry prepared by adding an α-form crystal to a saturated solution of α-form crystal of reduced glutathione and in a supersaturated solution of reduced glutathione, efficient production of α-form crystal, which is a desirable crystal form, is largely prevented by easy development of β-form crystal, which is a stable crystal. Under such circumstances, the development of a method for suppressing generation of β-type crystal and achieving selective crystallization to give α-type crystal in a supersaturated solution of reduced glutathione has been strongly desired.
On the other hand, as a method of controlling the development of crystal polymorphs of organic compounds including amino acid, addition of a habit modifier may sometimes be effective (patent document 1, non-patent document 2). However, for the habit modifier to function effectively, severe restrictions need to be met; for example, a compound added as a habit modifier needs to have a chemical structure extremely highly similar to that of the object compound (non-patent document 2), and further, a habit modifier needs to have a molecular weight the same as or slightly smaller than that of the object compound (non-patent document 3) and the like. Because of these restrictions, compounds with low structural similarity or compounds with molecular weights far apart from that of the object compound are generally excluded from the search targets of the habit modifier.
Regarding peptides composed of two or more amino acids such as reduced glutathione, an example in which development of crystal polymorphs is controlled by adding a habit modifier has not been known heretofore.